Justin Upton, Adam LaRoche and Mark Reynolds homered off the struggling right-hander in the first inning and the Arizona Diamondbacks went on to beat the Yankees 10-4 on Monday night in the opener of their three-game series.
Upton, who added a three-run homer in the eighth, reached base five times, had four RBIs and scored four runs.
Miguel Montero was 3 for 4 with a double and two RBIs as the Diamondbacks won at home for the 11th time in 16 games. They have lost 14 of 15 on the road.
Burnett (6-6) gave up seven runs and nine hits in four innings with no strikeouts and two walks.
"I don't feel like myself," he said. "I'm not having fun right now. Who would in a stretch like this? But the game is supposed to be fun. When you come out and take the air out of your team right away for a handful of starts it gets quite frustrating. I'm going to keep plugging away. It's just a matter of getting on a good roll."
Burnett has allowed 23 runs, including nine homers, in 20 innings in losing his last four starts.
"He's just not making his pitches is the bottom line," New York manager Joe Girardi said. "We'll get this corrected. We will, but right now he's just not making pitches."
The 33-year-old right-hander failed to make it past four innings for the second straight start and is 2-6 after opening the season a career-best 4-0.
"It's frustration at this point," Burnett said. "You know how good I am and how I should be throwing the ball, and the last past handful of starts I haven't given my team a chance out of the gate. I'm preparing, I'm doing my work in between, I'm just not executing out there in the game."
Upton would understand. The 22-year-old outfielder, with a new six-year, $51.25 million contract, has emerged from a horrific slump with a strong road trip. In addition to his third career two-homer game and first since May 20, 2009, he singled, walked and was hit by a pitch. He was in extreme pain after getting plunked in the elbow, but stayed in the game and feeling slowly returned to his arm. His next time up he iced the win with his 13th homer of the season.
"The last week or so I just told myself to go out there and be Justin Upton and whatever happens, happens," he said.
Rodrigo Lopez (3-6) gave up three runs and eight hits in eight innings for his first victory since May 15. He was 0-4 in his previous six starts. The Yankees knew Lopez well from his days with the Baltimore Orioles.
The Yankees, opening a six-game interleague trip to the West with their second regular-season visit to Arizona since their seven-game World Series loss to the Diamondbacks in 2001, got a run-scoring triple and sacrifice fly from Nick Swisher.
Alex Rodriguez had an RBI double in front of 47,229, Arizona's second-largest home crowd of the season. About half of them cheered for New York. Brett Gardner was 4 for 4 with two infield singles and a bunt single for the Yankees.
The big Yankee contingent in the crowd brought out the best in the Diamondbacks.
"We responded well to that energy," Arizona manager A.J. Hinch said. "I thought there was a ton of it from the beginning, even batting practice. It comes with playing the Yankees. ... They were fighting each other, Yankee fans and D-backs fans, and that produced an event, a great night that lifted up a lot of our players and they responded."
New York gave up 10 runs for the third time this season and dropped to 18-17 on the road. The Yankees' AL East lead fell to a half-game over idle Tampa Bay and Boston.
Three members of Arizona's 2001 World Series championship team -- Luis Gonzalez, Matt Williams and Mark Grace -- threw out the first pitch. ... Girardi said Phil Hughes (10-1) won't pitch in the six-game trip to Arizona and Los Angeles as part of the effort to hold down the right-hander's innings. Hughes turns 24 on Thursday. ... Arizona sends Dan Haren (7-5, 4.71 ERA) against the Yankees' Andy Pettitte (8-2, 2.47) on Tuesday night. ... The Yankees are 7-6 in interleague play. ... The Diamondbacks have hit three home runs in an inning 18 times in their history, three this season. They have never hit four in an inning.